The broad long-term objective of this research project is the study of the correlation between variation in neuroanatomical features of the human brain and neuropsychological characteristics. A main question concerns whether neuroanatomical asymmetry is related to patterns of hemispheric functional asymmetry. Their association has not been demonstrated, although often assumed. The proposed work is aimed to testthis issue. The method designed to achieve the overlap objectives involves testing seriously ill patients with a battery of neuropsychological tests while they are still ambulatory and feeling well. In the event of death, a clinical autopsy for postmortem study of the brain is requested. The subjects recruited to the project are carefully selected and they consent to both aspects of the project. The subjects are tested with psychologicalmeasures including IQ and memory tests, perceptual and motoric tasks of functional asymmetry, tests of verbal and spatial ability, and measures of personality. Anatomy is studied via numerous baseline measures ofweights, volumes and caliper measures o.f specific structures and quantitative histological analyses of specific cytoarchitectonic regions. The specific aims of the application include the following: (1) Study of the relationship between anatomy of the corpus callosum and a perceptual measure of functional asymmetry for language in a group of 45 men and women in order to test the hypothesis that variation in callosal anatomy is related to functional asymmetry; (2) Study of the anatomy of the planum temporale (PT) (a gyral surface of the temporal operculum within the Sylvian fissure) in relation to hand preference and sex in a group of 67 brains, to help resolve a long-standing issue regarding its role in functional asymmetry; (3) multivariate statistical analyses of multiple behavioral and anatomical variables with the aim of testing specific hypotheses providing the beginning of a quantitative model of structure-function relationships in temporo-parietal regions;(4) Studies of numerical densities of neurons in left and right PT to assess microscopic correlates of behavior and subject characteristics. This research has relevance for the origin of functional lateralization and for possible etiological factors of clinical disorders, such as developmental dyslexia and schizophrenia which may involve atypical lateralization. Study of histological differences between right and left temporal association cortex may shed light on the severe and long-lasting deficits in patients who suffer unilateral brain damage in these regions. Neurobiological bases of sex differences in cognition and in response to brain damage may be elucidated. The results of this research may provide guidelines for MR brain imaging studies done in the clinic or in research., The brain specimens collected have been made available to other investigators and may prove -useful as control specimens for studies of brains from people with various neuropsychiatric disorders.